PROJECT SUMMARY/ABSTRACT: Core C The role of the Protein and Small Molecule Chemistry Core is central to the needs of all the investigators in the Program Project Proposal. The Core will provide project investigators access to purified proteins and virus-like particle (VLPs) as well as custom synthesis of small molecules and peptides. The Core will also construct mutant versions of proteins by site-directed mutagenesis as needed by investigators. Finally, the Core will characterize and quantitate protein-protein and protein-ligand interactions. Examples of Core activities include purification of norovirus protease to facilitate drug discovery and purification of VLPs for investigations of antibody interactions with capsid. Activities also include synthesis of small molecule protease inhibitor candidates for biochemical and cell-based testing as well as structural studies. In addition, the Core will measure binding affinity of small molecules with norovirus protease as well as affinity of antibody-VLP interactions and other protein-protein interactions as needed by project investigators. Finally, the Core will construct site-directed mutations in the norovirus protease, p22, and p41 genes and others as needed for functional studies by project investigators. The Core personnel have extensive experience in the methods required for providing these services and all of the equipment and resources necessary are available in the Core. The performance of services such as protein purification and small molecule synthesis, mutagenesis, and binding measurements in a Core facility avoids the need for individual investigators to acquire the necessary expertise and equipment and is an efficient means of facilitating progress on the scientific goals of the project.